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Contains fulltext : 91735.pdf (Publisher’s version ) (Closed access)

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Contains fulltext : 95827.pdf (publisher's version ) (Closed access), A synergistic relationship is thought to exist between hypothalamic-pituitary-adrenal (HPA) axis activity and dopamine neurotransmission. To test whether a high response to dopamine indeed implies a hyperactive HPA-axis, we here used Wistar rats that were selected twice independently (original and replicate lines) for a high or low susceptibility to the dopamine receptor agonist apomorphine (so-called APO-SUS and APO-UNSUS rats, respectively). The APO-SUS rats from the original line displayed a hyperactive HPA-axis in that higher basal and stress-induced adrenocorticotropic hormone (ACTH) levels, and lower basal free-corticosterone levels were observed than those found in the original APO-UNSUS rats. In contrast, the activity of the HPA-axis in the APO-SUS rats from the replicate line did not differ from that in the replicate APO-UNSUS rats. Thus, in the APO-SUS/APO-UNSUS rat model the level of HPA-axis activity is not necessarily causally linked to dopamine responsiveness, implying that a hyperactive HPA-axis is not a prerequisite for a high dopaminergic response.

Radboud Universiteit Nijmegen, 17 december 2010, Promotor : Martens, G.J.M., Contains fulltext : 83777.pdf (Publisher’s version ) (Open Access)

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Contains fulltext : 69125.pdf (publisher's version ) (Open Access)

Contains fulltext : 35175.pdf (publisher's version ) (Closed access), Interleukin-12 (IL-12) is the founding member of a rapidly growing family of heterodimeric cytokines. It consists of two subunits, designated p35 and p40 that together constitute a disulphide-linked heterodimeric cytokine. IL-12 is well known for its prominent role in both the early innate immune response and the skewing of the ensuing acquired immune response towards Th1. Here, we report the presence of IL-12p35 and three highly distinct IL-12p40 genes in common carp (Cyprinus carpio). The carp is a bony fish species genetically similar to the zebrafish, but its substantially larger body size facilitates immunological studies. A comparison of IL-12p35 genes of mammalian and non-mammalian species reveals the presence of a duplicated exon that is unique to the mammalian lineage. The organisation of the three carp IL-12p40 genes is similar to that of higher vertebrates. Phylogenetic analyses that include the p40-related subunits of other composite cytokines confirm the presence of three genuine IL-12p40 genes in carp and indicate that they are evolutionary ancient and possibly not restricted to bony fishes. The orthology of the different carp p40 subunits to mammalian IL-12p40 is further evident from the conservation of key residues involved in the formation of intra- and interchain disulphide bridges and the tight interlocking topology between p35 and p40. The expression of each of the carp IL-12p40 genes differs profoundly, constitutively as well as in response to in vitro stimulation of carp macrophages. Collectively, the presence of multiple and substantially different IL-12 genes signifies a considerable expansion of the vertebrate heterodimeric cytokine family.

Contains fulltext : 32760.pdf (publisher's version ) (Closed access), Interleukin-11 (IL-11) is a key cytokine in the regulation of proliferation and differentiation of hematopoietic progenitors and is also involved in bone formation, adipogenesis, and protection of mucosal epithelia. Despite this prominent role in diverse physiological processes, IL-11 has been described in only four mammalian species, and recently, in rainbow trout (Oncorhynchus mykiss). Here we report the presence of IL-11 in common carp (Cyprinus carpio), a bony fish species related to zebrafish. IL-11 is expressed in most carp organs and tissues. In vitro expression of IL-11 in cultured macrophages is enhanced by stimulation with lipopolysaccharide and is markedly inhibited by cortisol. A detailed and systematic scan of several fish genome databases confirms that IL-11 is present in all fish, but also reveals the presence of a second, substantially different IL-11 gene in the genomes of phylogenetically distant fish species. We designated both fish paralogues IL-11a and IL-11b. Although sequence identity between fish IL-11a and IL-11b peptides is low, the conservation of their gene structures supplemented by phylogenetic analyses clearly illustrate the orthology of both IL-11a and IL-11b genes of fish with mammalian IL-11. The presence of IL-11 genes in fish demonstrates its importance throughout vertebrate evolution, although the presence of duplicate and divergent IL-11 genes differs from the single IL-11 gene that exists in mammals.